The field of the invention is cartilage degradation.
Hyaline cartilage, which covers the articular ends of the bones, contains primarily proteoglycans in its intracellular matrix. The breakdown of these proteoglycans in arthritic diseases, such as osteoarthritis and rheumatoid arthritis, leads to loss of the capacity of cartilage to resist wear. Proteoglycan aggregate, which has a high molecular weight, comprises three portions - namely, the proteoglycan subunit, hyaluronic acid, and link protein. The proteoglycan subunit comprises chondroitin sulfate and keratan sulfate chains, which are attached to a protein core. Chondroitin sulfate, keratan sulfate and hyaluronic acid are glycosaminoglycans, polysaccharides comprising two different sugar residues that alternate regularly in the polysaccharide chain.
The arthritides, for example osteoarthritis, are not a single nosologic entity, but rather a group of disorders that have in common the mechanical destruction of a joint. The biochemical changes in osteoarthritis primarily involve proteoglycans. There is a decrease in proteoglycan content and aggregation, as well as a decrease in the chain length in the glycosaminoglycans. Compared to the level in normal articular cartilage, keratan sulphate is decreased and chondroitin sulfate is increased. In the early stages of osteoarthritis, synthesis of matrix by chondrocytes is augmented, presumably as a reparative action As the osteoarthritis progresses, protein synthesis declines, suggesting that the cell reaches a point where it fails to respond to reparative stimuli. Levels of proteases in the cartilage increase, and active proteolytic enzymes not normally found in cartilage can be detected.
Rheumatoid arthritis is a systemic, chronic, inflammatory disease that involves the joints and, like osteoarthritis, comprises a heterogeneous group of disorders. While many of the pathological changes in rheumatoid arthritis are distinct from those in osteoarthritis, a common feature is degradation of cartilage, particularly loss of proteoglycans. Drugs used to treat rheumatoid arthritis primarily suppress the inflammatory processes that contribute to the pathology.
At present, there is no specific treatment for arresting degradation of cartilage in humans with arthritic diseases.